BIOMEDICAL RESEARCH COMPONENT (RESEARCH BASE) 1. Evolution of Digestive Disease-Related Research Programs at CWRU and the CCF: Both Case Western Reserve University (CWRU) and the Cleveland Clinic Foundation (CCF) have a long history and tradition of excellence in digestive diseases. Dr. Michael Sivak, former Chief of Gastrointestinal & Liver Diseases at University Hospital Case Medical Center (UHCMC), was recruited to CWRU in 1990 to build a strong program in clinical and basic research. He then recruited Dr. Claudio Fiocchi, an internationally renowned investigator in IBD, to become the Director of Research for the Division. Over the next decade, they together developed an outstanding clinical and research program in digestive diseases, including NIH-funded research in endoscopy, Barrett's esophagus, and IBD. During this same period. Dr. Joel Richter, former Chairman of Gastroenterology at the CCF, developed one of the premier clinical and translational Gl programs in the country, with a focus on upper Gl/motility, IBD and hepatology. As a result of this effort, the Cleveland Clinic has been ranked #2 in Gastroenterology and Hepatology by US News & World Report for more than two decades. In 2002, the CCF and CWRU formed an academic partnership for teaching and research by establishing the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University (CCLCM). With this affiliation agreement came the opportunity for all investigators and educators at the CCF to become CWRU faculty, underscoring the high level of institutional collaboration between the institutions. Following the retirement of Dr. Sivak from CWRU in 2006, Dr. Fiocchi was recruited to the CCF to develop the basic research component of their Digestive Diseases Institute. At the same time. Dr. Art McCullough, a leading translational researcher in liver diseases, became Chairman of the Department of Gastroenterology, and recruited Dr. Laura Nagy, a leading expert in alcoholic liver disease, to further develop the basic research liver program at the CCF. In 2008, Dr. Fabio Cominelli was recruited as Chief of the Division of Gastrointestinal & Liver Disease at CWRU and Director of the new Digestive Health Institute at CWRU/UHCMC to further develop the clinical, research, and education components of the digestive diseases program. At the same time. Dr. Theresa Pizarro, a renowned mucosal immunologist with expertise in intestinal cytokine biology, was recruited to the Department of Pathology at CWRU to develop a basic science mucosal immunology program. In 2010, Dr. John Fung, an internationally renowned liver transplant surgeon and transplantation researcher became Director of the Digestive Diseases Institute at the CCF and appointed Dr. Art McCullough as his Vice-Chair for Research in order to create a more comprehensive multi-disciplinary approach to digestive diseases research at CCF. The same year, Dr. Cominelli at CWRU and Dr. Fiocchi at the CCF firmly cemented an unprecedented academic environment of cross-institutional collaboration in digestive diseases between their neighboring institutions by successfully obtaining an NIH-funded T32 Combined Training Program in Digestive Diseases, which they co-direct, thus allowing the best post-doctoral trainees to choose from more than 20 mentors at both institutions. This group of investigators constitutes the leadership team for the proposed Cleveland DDRCC. Further cementing this high-level commitment to cross institutional collaboration. Dr. Cominelli at CWRU and Dr. Fung at CCF have jointly developed strong collaborative efforts focused on promoting digestive disease research in Cleveland by funding several initiatives, including $300,000 in seed funds to develop this current Silvio O. Conte P30 application (a one-time investment to support development of the core laboratories and five pilot/feasibility projects). Notably, prior to Dr. Cominelli's arrival at CWRU in 2008, he successfully developed an outstanding multidisciplinary program at the University of Virginia, which included several new clinical programs, a program project on the immunogenetics of experimental IBD, and a Silvio O. Conte P30 DDRCC, which began its funding in 2003 and which he directed until the time of his relocation to CWRU in 2008. The current proposal to establish a unique, cross-institutional Silvio O. Conte Cleveland Digestive Diseases Research Core Center (DDRCC) at Case Western Reserve University and the Cleveland Clinic Foundation is the culmination of a conceptual framework conceived by Dr. Comingle at CWRU and Dr. Fiche at the CCF, both of whom have been collaborating for more than two decades. The proposed DDRCC builds on Dr. Cominelli's extensive previous experience establishing and administering a Silvio O. Conte DDRCC program, as well three years of work led by Drs. Cominelli and Fiocchi to assemble a strong Research Base ($16.7 million in federally-funded grants) across both their neighboring institutions.